Introduction: High prion protein (PrP) levels are associated with breast, colon and gastric cancer resistance to treatment and with a poor prognosis for the patients. However, little is known about the underlying molecular mechanism(s) regulating human PrP gene (PRNP) expression in cancers. Because endoplasmic reticulum (ER) stress is associated with solid tumors, we investigated a possible regulation of PRNP gene expression by ER stress.

Figure 9: PrP does not prevent ER stress-mediated Bax activation in MCF-7 cells. Western blot assessing the impact of PrP silencing on Bax activation as well as Bim and Bcl-2 levels at 6, 12 or 18 h following a 6-h treatment with Brefeldin A (A), Tunicamycin (B), or Thapsigargin (C). Western blot using the 3F4 antibody confirms ER stress-induced increase in PrP levels as well as its efficient siRNA-mediated silencing, while probing for Bax and β-actin controls for equal protein input and protein loading, respectively. (D) MCF-7 cells transfected with a second siPrP and treated for 18 h with ER stressor; experiments performed as described in A-C.

Mentions:
We have previously discovered that PrP can inhibit Bax-mediated cell death [2,4]. Immunoprecipitation of the pro-apoptotic 6A7-immunoreactive form of Bax indicated that BFA, TM and Thps all induce Bax activation (Figure 9A-C). However, silencing PrP before ER stress did not increase the level of Bax activation indicating that PrP cannot prevent ER stress-induced Bax activation and that PrP delays ER stress-mediated cell death by another mechanism.

Figure 9: PrP does not prevent ER stress-mediated Bax activation in MCF-7 cells. Western blot assessing the impact of PrP silencing on Bax activation as well as Bim and Bcl-2 levels at 6, 12 or 18 h following a 6-h treatment with Brefeldin A (A), Tunicamycin (B), or Thapsigargin (C). Western blot using the 3F4 antibody confirms ER stress-induced increase in PrP levels as well as its efficient siRNA-mediated silencing, while probing for Bax and β-actin controls for equal protein input and protein loading, respectively. (D) MCF-7 cells transfected with a second siPrP and treated for 18 h with ER stressor; experiments performed as described in A-C.

Mentions:
We have previously discovered that PrP can inhibit Bax-mediated cell death [2,4]. Immunoprecipitation of the pro-apoptotic 6A7-immunoreactive form of Bax indicated that BFA, TM and Thps all induce Bax activation (Figure 9A-C). However, silencing PrP before ER stress did not increase the level of Bax activation indicating that PrP cannot prevent ER stress-induced Bax activation and that PrP delays ER stress-mediated cell death by another mechanism.

Introduction: High prion protein (PrP) levels are associated with breast, colon and gastric cancer resistance to treatment and with a poor prognosis for the patients. However, little is known about the underlying molecular mechanism(s) regulating human PrP gene (PRNP) expression in cancers. Because endoplasmic reticulum (ER) stress is associated with solid tumors, we investigated a possible regulation of PRNP gene expression by ER stress.